1. Field
The present disclosure relates generally to the fields of cardiology, developmental biology and molecular biology. More particularly, it concerns gene regulation and cellular physiology in cardiomyocytes and skeletal muscle cells. Specifically, the disclosure relates to the use of an miRNA to reprogram cardiac fibroblasts into cardiomyocytes and the use of such miRNA in the prevention of scarring and repair in post-myocardial infarction, and in treating myotonic dystrophy, muscular dystrophy and muscle degenerative diseases.
2. Description of Related Art
Heart failure is one of the leading causes of death in the United States. Because human hearts lack regenerative capacity, cardiomyocyte loss due to a variety of reasons eventually results in loss of pump function and heart failure. Heart transplantation is a valid cure but limited by the availability of donors. This situation calls for approaches to help cardiomyocyte regeneration after injury.
Cell replacement therapy is a focus area in new approaches for treating heart failure. Over the years, peripheral blood, bone marrow cells, skeletal muscle, adipose and ES/iPS-derived cells have been used in efforts to rescue injured hearts, in hope that these cells can trans-differentiate or differentiate into cardiomyocytes (Garbern and Lee, 2013). Though a functional improvement is often seen, it is hardly attributed to new cardiac muscle formation, but conditioning of the microenvironment.
More recently, Olson's and Srivastava's groups independently demonstrated 3-4 transcription factors can directly convert cardiac fibroblasts into cardiomyocytes in vivo, and improve recovering after ischemic heart injury (Qian et al., 2012 and Song et al., 2012). These efforts have laid a foundation for further developing similar reprogramming-based regimens. Among remaining challenges, safe and effective delivering of several transcription factors is still difficult.